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Signaling Pathways and MicroRNA Changes in Nano-TiO2 Treated Human Lung Epithelial (BEAS-2B) Cells

Sheau-Fung Thai, Kathleen A Wallace, Carlton P Jones

    Journal of Nanoscience and Nanotechnology
    |September 3, 2015
    PubMed

    Insights

    Titanium dioxide nanoparticles (nano-TiO2) alter gene and microRNA expression in human lung cells, impacting pathways linked to cancer. These nano-TiO2 effects on lung cells reveal potential risks and cellular responses.

    Area of Science:

    • Nanotoxicology
    • Molecular Biology
    • Cell Biology

    Background:

    • Titanium dioxide nanoparticles (nano-TiO2) are widely used, necessitating an understanding of their biological effects.
    • Human lung epithelial cells (BEAS-2B) are a relevant model for studying nanoparticle inhalation and lung toxicity.
    • Gene expression analysis, including messenger RNA (mRNA) and microRNA (miRNA), is crucial for elucidating cellular responses to nanomaterials.

    Purpose of the Study:

    • To investigate the effects of nano-TiO2 on mRNA and miRNA expression in human lung epithelial cells.
    • To identify the specific cellular pathways and signaling networks affected by nano-TiO2 treatment.
    • To explore the potential role of altered miRNA expression in nano-TiO2-induced cellular responses and tumorigenesis.

    Main Methods:

    • BEAS-2B cells were exposed to varying concentrations of nano-TiO2 (0-100 μg/ml).
    • mRNA and miRNA expression profiles were analyzed using Affymetrix microarrays after 1 and 3 days of exposure, respectively.
    • Bioinformatic tools (MetaCore, IPA) were employed to analyze differentially expressed genes and miRNAs and to identify affected canonical/signaling pathways.

    Main Results:

    • Nano-TiO2 treatment, even at non-cytotoxic doses, significantly altered both mRNA and miRNA expression patterns.
    • Affected pathways included cell cycle regulation, apoptosis, oxidative response, signaling pathways (RAS, PI3K/AKT), and inflammatory response.
    • Specifically, the oncogenic miR-17-92 cluster was upregulated, while the tumor suppressor let-7 miRNA family was downregulated, particularly in the let-7/KRAS signaling pathway.

    Conclusions:

    • Nano-TiO2 exposure induces widespread and coordinated alterations in gene and miRNA expression in human lung cells.
    • The observed changes in miRNA expression, including the modulation of the miR-17-92 cluster and let-7 family, provide a mechanistic link to observed mRNA changes.
    • These findings suggest that in vitro nano-TiO2 exposure can lead to pathway alterations relevant to in vivo tumorigenesis, highlighting potential health risks.

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